study of mk-1248 with and without pembrolizumab (mk-3475) for participants with advanced solid tumors (mk-1248-001)

Conditions: Advanced Solid Tumor

Summary: in this study, participants with advanced solid tumors were assigned to receive escalating doses of either mk-1248 alone or mk-1248 in combination with pembrolizumab (mk-3475). this study used the number of dose-limiting toxicities (dlts) at each dose level to find and confirm the maximum tolerated dose (or maximum administered dose) for mk-1248 alone and in combination with pembrolizumab.


Eligibility criteria:
inclusion criteria: * histologically- or cytologically-confirmed metastatic solid tumor for which there is no available therapy that may convey clinical benefit * measurable disease by response evaluation criteria in solid tumors (recist) 1.1 criteria * performance status of 0 or 1 on the eastern cooperative oncology group (ecog) performance scale * adequate organ function * female participants of childbearing potential should be willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication * male participants should agree to use adequate contraception starting with the first dose of study therapy through 180 days after the last dose of study medication * can submit a baseline tumor sample exclusion criteria: * has had chemotherapy, radiation, or biological cancer therapy within 4 weeks prior to the first dose of study medication, or not recovered from adverse events due to cancer therapeutics administered more than 4 weeks earlier * currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study medication * previous treatment with another agent targeting the glucocorticoid-induced tumor necrosis factor receptor-related protein (gitr) receptor * previous treatment with an immunomodulatory therapy and was discontinued from that therapy due to an immune-related adverse event * expected to require any other form of antineoplastic therapy while on study * on chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication * history of a previous, additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years with the exception of successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer * known active central nervous system (cns) metastases and/or carcinomatous meningitis * severe hypersensitivity reaction to treatment with another monoclonal antibody * active autoimmune disease or a documented history of autoimmune disease with the exception of vitiligo or resolved childhood asthma/atopy, or endocrine deficiency following treatment with an immunomodulatory agent * active infection requiring therapy * active or a history of non-infectious pneumonitis * prior stem cell or bone marrow transplant * known history of human immunodeficiency virus (hiv), active chronic or acute hepatitis b or c * known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study * regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol), at the time of signing informed consent * symptomatic ascites or pleural effusion * pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study through 180 days after the last dose of study medication * major surgery within 16 weeks prior to screening * live vaccine within 30 days prior to first dose of study medication

Keywords: solid tumor pd1 pd-l1 pdl1